EP4023147B1 - Verfahren zur analyse einer probe durch zeitlich aufgelöste messung der intensität von rückgestreuten photonen - Google Patents

Verfahren zur analyse einer probe durch zeitlich aufgelöste messung der intensität von rückgestreuten photonen Download PDF

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EP4023147B1
EP4023147B1 EP21217909.7A EP21217909A EP4023147B1 EP 4023147 B1 EP4023147 B1 EP 4023147B1 EP 21217909 A EP21217909 A EP 21217909A EP 4023147 B1 EP4023147 B1 EP 4023147B1
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time
layer
biological tissue
elementary
photons
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French (fr)
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EP4023147A1 (de
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Anne Planat-Chretien
Michel Berger
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Commissariat a lEnergie Atomique et aux Energies Alternatives CEA
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Commissariat a lEnergie Atomique CEA
Commissariat a lEnergie Atomique et aux Energies Alternatives CEA
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/02—Detecting, measuring or recording pulse, heart rate, blood pressure or blood flow; Combined pulse/heart-rate/blood pressure determination; Evaluating a cardiovascular condition not otherwise provided for, e.g. using combinations of techniques provided for in this group with electrocardiography or electroauscultation; Heart catheters for measuring blood pressure
    • A61B5/02007—Evaluating blood vessel condition, e.g. elasticity, compliance
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/02—Detecting, measuring or recording pulse, heart rate, blood pressure or blood flow; Combined pulse/heart-rate/blood pressure determination; Evaluating a cardiovascular condition not otherwise provided for, e.g. using combinations of techniques provided for in this group with electrocardiography or electroauscultation; Heart catheters for measuring blood pressure
    • A61B5/026—Measuring blood flow
    • A61B5/0261—Measuring blood flow using optical means, e.g. infrared light
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/44—Detecting, measuring or recording for evaluating the integumentary system, e.g. skin, hair or nails
    • A61B5/441—Skin evaluation, e.g. for skin disorder diagnosis
    • A61B5/445—Evaluating skin irritation or skin trauma, e.g. rash, eczema, wound, bed sore
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/48—Other medical applications
    • A61B5/4887—Locating particular structures in or on the body
    • A61B5/489—Blood vessels

Definitions

  • the technical field of the invention is the application of optical measurements to monitoring the vascularization of a subcutaneous flap, having been buried under the skin of a person as part of reconstructive surgery.
  • a possible surgical technique is to use a pedicled flap.
  • a flap is a fragment of skin and subcutaneous cellular tissue, taken from another part of the body, and presenting autonomous vascularization, passing through a pedicle.
  • the flap is buried under the original skin to reconstruct the volume of the breast.
  • the pedicle is then connected to a vein and an artery, so as to allow irrigation of the flap.
  • DRS Diffuse Reflectance Spectroscopy
  • DRS Diffuse Reflectance Spectroscopy
  • Light propagation properties generally include absorption properties and/or light scattering properties. These include absorption or diffusion coefficients, the latter representing respectively absorption and diffusion probabilities of a photon per unit length.
  • the estimation of the propagation properties of light, at certain wavelengths, allows an estimation of a concentration of analytes in the analyzed medium.
  • the DRS can be used to estimate an oxygenation rate of superficial tissues, by a comparison between a quantity of oxyhemoglobin and a quantity of total hemoglobin (oxyhemogoblin + deoxyhemoglobin).
  • the delayed photons pass through each superimposed layer.
  • the resulting signal from the delayed photons depends on both the optical properties of the surface and deep layers. In order to correctly characterize the deep layers, the contribution of the surface layers to the detected signal must be taken into account.
  • the inventors propose a method, based on TRS, allowing post-operative monitoring of the vascularization of a flap.
  • the method is non-invasive. It can allow an estimation of the concentration of hemoglobin or oxyhemoglobin in the flap.
  • the light source is a laser source.
  • FIG. 1A represents a device 1 allowing monitoring of the vascularization of a flap buried under a layer of skin.
  • the objective is to determine the occurrence of venous or arterial occlusion, particularly during the first hours or days after surgery.
  • the device comprises a pulsed light source 10. It is configured to emit a pulsed light beam 11, the duration of each pulse typically being between 1 ps and 100 ps.
  • the pulse frequency can for example be between 1 and 100 MHz.
  • the light beam 11, called the illumination beam, propagates towards a sample of biological tissue 20 to be analyzed.
  • the sample 20 is delimited by a surface 21.
  • the intersection of the illumination beam 11 and the surface 21 of the sample forms an illumination zone 12, spatially delimited.
  • the illumination zone is preferably punctual: it is by example inscribed in a circle with a diameter less than 1mm, or even less than a few hundred ⁇ m, for example 100 ⁇ m or 1 mm.
  • the elementary illumination zone 12 is represented on the Figure 1B .
  • the light source can be placed in contact with the biological tissue 20 or at a distance from the latter.
  • the light source is a femtosecond laser light source.
  • the light source is placed at a distance from the sample.
  • the light beam 11 is transported to the surface 21 of the sample by an optical illumination fiber 10'.
  • the photons forming the illumination beam 11 propagate in the biological tissue to be analyzed.
  • the biological tissue 20 is formed of a diffusing medium, capable of absorbing photons, the properties of photon propagation in the medium depending in particular on absorption or diffusion properties in the medium.
  • the absorption properties can be quantified by a linear absorption coefficient ⁇ a ( ⁇ ) .
  • the linear absorption coefficient quantifies a probability of absorption by the medium per unit length, at the wavelength ⁇ . It is usually expressed in cm -1 .
  • Scattering properties can be quantified by a diffusion coefficient ⁇ s ( ⁇ ) or a reduced diffusion coefficient ⁇ s ' ( ⁇ ), which quantify a probability of scattering from the medium per unit length, at the wavelength ⁇ . It is usually expressed in cm -1 .
  • the device comprises a photodetector 16. It may for example be a photomultiplier tube, of the hybrid photomultiplier tube type, usually designated by the acronym HPM (Hybrid Photo Multiplier - Hybrid Photomultiplier).
  • HPM Hybrid Photo Multiplier - Hybrid Photomultiplier
  • the photons detected by the photodetector 16 emanate from an elementary detection zone 14 on the surface 21 of the sample 20.
  • the elementary detection zone 14 is preferably punctual, being, like the elementary zone of illumination 12, inscribed in a diameter less than 1 mm or even 250 ⁇ m.
  • the elementary detection zone 14 is merged with or separated from the elementary illumination zone 12.
  • the distance between the elementary illumination zone 12 and the elementary detection zone 14 is a backscattering distance d r . It can be a few centimeters or of the order of a centimeter, or even less than 1 cm.
  • the photons 13 emanating from the sample, through the elementary detection zone 14, are photons backscattered by the sample according to the backscattering distance d r .
  • the photodetector 16 can be placed in contact with or at a distance from the sample 20.
  • an optical detection fiber 16' transports the backscattered photons 13 between the elementary detection zone 14 and the photodetector 16.
  • the light source 10 can be monochromatic or polychromatic.
  • the light source is a super-continuum (supercontinuous) type femtosecond laser emitting light pulses at a frequency of 80 MHz.
  • a selection of the illumination wavelength ⁇ i is carried out by an optical filter 10 f .
  • the filter 10 f is a filter wheel comprising different band-pass interference filters allowing selection of the illumination wavelength according to one of the following values: 750 nm, 800 nm or 850 nm .
  • the 10 f filter can also include high-pass filtering, in addition to the band-pass interference filters.
  • two illumination wavelengths ⁇ 1 and ⁇ 2 are used which correspond to absorption wavelengths of deoxyhemoglobin and oxyhemoglobin.
  • ⁇ 1 750 nm
  • ⁇ 2 850 nm.
  • the notation ⁇ i designates indifferently an illumination wavelength, whether it is ⁇ 1 or ⁇ 2 .
  • the photodetector 16 is connected to an electronic counting card 17 of the TCSPC (Time-Correlated Single Photon Counting) type.
  • TCSPC Time-Correlated Single Photon Counting
  • This type of electronic counting card is well known in the field of time-resolved optical measurements.
  • the counting card establishes a temporal distribution I ( ⁇ i ) of the photons detected by the photodetector 16.
  • the temporal distribution is established statistically following a multitude of light pulses emitted successively by the light source 10.
  • the temporal distribution I ( ⁇ i ) corresponds to a histogram representing a number of backscattered photons 13 detected (y-axis) as a function of time (x-axis).
  • the counting card 17 is connected to a processing unit 18.
  • the processing unit 18 comprises a microprocessor programmed to implement the steps described below, in connection with the Figure 3 , from the temporal distributions I ( ⁇ i ) established by the counting card 17.
  • the device may include one or more optical attenuators, each optical attenuator usually being designated “optical density”. Those skilled in the art adapt the attenuation according to the power of the light source and the sensitivity of the photodetector.
  • the counting card 17 is synchronized by a synchronization line 15, which detects each light pulse emitted by the light source 10. This makes it possible to determine a time interval dt between the emission and the detection of each photon detected by the photodetector 16.
  • a light pulse of incident photons 11 occurring at an illumination instant t 10
  • a temporal distribution of backscattered photons 13 the latter extending over a temporal interval ⁇ t 13 .
  • FIG. 1D represents a configuration according to which the light source 10 is connected to five optical illumination fibers 10', via an optical switch (optical switch).
  • the optical illumination fibers 10' are distributed respectively in the center and in the middle of the sides of a square of side 12 mm.
  • the device 1 comprises four optical detection fibers 16', respectively connected to four different photodetectors 16.
  • the optical detection fibers 16' are respectively arranged on the four corners of the square of side 12 mm previously described.
  • Such a configuration makes it possible to address backscatter distances equal to 6 mm, 8.5 mm and 13.4 mm respectively.
  • the power of the incident light source is monitored by sampling the excitation light provided by a 15' optical fiber.
  • each time interval d ⁇ w extends around a detection instant ⁇ w .
  • the segmentation of the temporal distribution makes it possible to estimate a number of photons detected during each temporal interval d ⁇ w , which corresponds to a temporal intensity I w ( ⁇ i ) for each temporal interval d ⁇ w .
  • the index w is an integer corresponding to the rank w of each time interval with 1 ⁇ w ⁇ N w , N w being the number of time intervals considered.
  • the duration of each time interval d ⁇ w can be less than a nanosecond, for example being of the order of a few tens of ps.
  • each time interval d ⁇ w corresponds to a depth d w capable of being reached by the photons in each layer of the sample 20.
  • the depth d w is determined relative to the surface 21 of the sample, comprising the elementary illumination zone 12.
  • ⁇ w can be associated with a layer elementary l w of rank w extending to a depth d w ⁇ ⁇ /2, where ⁇ is the thickness of the elementary layer, which depends on the width of the temporal interval d ⁇ w considered.
  • the device is configured to allow detection of a venous or arterial occlusion in a flap buried under a layer of skin.
  • the device is applied against the surface 21 of a biological tissue 20, the latter comprising a superficial layer 20 1 of skin and a deep layer 20 2 .
  • the superficial layer is interposed between the surface of the tissue and the deep layer.
  • hemoglobin is meant the two states of hemoglobin, namely oxyhemoglobin and deoxyhemoglobin.
  • Two illumination wavelengths are successively used which correspond to wavelengths absorbed by oxyhemoglobin and deoxyhemoglobin.
  • a layer corresponds to a macroscopic part of the sample in which the optical properties are considered homogeneous.
  • An elementary layer corresponds to a “microlayer”, whose thickness and depth depend on the temporal segmentation carried out on the temporal distribution.
  • the surface layer and the deep layer are separated from each other by an interface 20 1/2 .
  • the interface is located at an interface depth d 1/2 relative to the surface 21 of the sample.
  • the interface depth is not known.
  • the interface depth d 1/2 can be located at a few mm, for example 3 mm or 5 mm, at a few cm, for example 1 or 2 cm, relative to the surface 21 of the sample.
  • FIG. 3 schematizes the main steps of the process, in an application case for which we seek to determine the occurrence of a venous or arterial occlusion in the deep layer of the biological tissue examined. These are steps 100 to 130.
  • the method can also allow identification of a detected occlusion: the question is whether the occlusion is venous or arterial. This corresponds to steps 140 and 150.
  • steps 140 and 150 we seek to estimate a variation in the concentration ⁇ c k of hemoglobin 22 k , relative to a reference concentration c k,ref .
  • the reference concentration corresponds to a concentration of hemoglobin at a reference time T ref .
  • T ref a concentration of hemoglobin at a reference time.
  • An important aspect of the invention is to be able to determine a variation in concentration of oxyhemoglobin and deoxyhemoglobin (or at least a quantity proportional to each variation) in the deep layer, without it being necessary to determine the variation in concentration of oxyhemoglobin and deoxyhemoglobin in the superficial layer.
  • the device thus makes it possible to carry out time-resolved optical reflectance measurements which can enable monitoring of the oxygenation of the flap, in a non-invasive manner.
  • the principle of the invention is schematized on the Figures 4A and 4B .
  • the Figure 4A we have represented the sample, with the photons respectively coming from the surface layer 20 1 and the deep layer 20 2 .
  • the response of the deep layer to the illumination beam varies. This results in a variation of the backscattered signal.
  • This signal is sensitive to variations in the deep layer, but also in the superficial layer: if the superficial layer evolves (due to surgery for example), then the backscattered signal will reflect the evolution of the two layers; to be able to correctly detect and identify the occlusion occurring in the deep layer, it is necessary to correct this signal for the contribution of the superficial layer: this is the object of the invention.
  • a first objective of the invention is described in connection with steps 100 to 130 described below: this involves detecting the occurrence of a venous or arterial occlusion in the deep layer 20 2 , knowing that the depth of the The interface 20 1/2 between the two layers is not known.
  • a second objective is to monitor the concentration of oxyhemoglobin or oxyhemoglobin in the deep layer 20 2 . This corresponds to steps 140 and 150.
  • Step 100 acquisition
  • the sample 20 is illuminated in an impulse manner. From backscattered photons 13 detected by the photodetector 16 after each pulse, a temporal distribution I ( ⁇ i ) is constituted at each emission wavelength ⁇ .
  • Step 100 can be carried out sequentially or simultaneously for several wavelengths ⁇ i , so as to obtain, for each wavelength, a temporal distribution I ( ⁇ i ).
  • the index i designates the rank of each wavelength.
  • the temporal distribution I ( ⁇ i ) represents an evolution of an intensity of the backscattered photons detected by the photodetector 16, as a function of time.
  • the intensity can be normalized by the intensity I 10 emitted by the source of light 10.
  • a fiber, called excitation return extends between the light source 10 and a photodetector 16. Such normalization makes it possible to take into account the fluctuations of the light source.
  • intensity designates indifferently an intensity or an intensity normalized by the intensity I 10 of the illumination beam.
  • step 100 is implemented at different measurement times T, so as to allow regular monitoring of the sample examined. It is notably implemented at a reference instant T ref , during which the sample examined is considered to be in a reference state.
  • T ref a reference time distribution I ref ( ⁇ i ) is obtained at each wavelength ⁇ i .
  • I T ( ⁇ i ) the temporal intensity distribution is denoted I T ( ⁇ i ) .
  • Step 110 determination of temporal intensities.
  • each temporal distribution I T ( ⁇ i ) is decomposed into time windows, so as to obtain a temporal intensity I w , T ( ⁇ i ) of backscattered photons detected in the time interval d ⁇ w at wavelength ⁇ i .
  • the term temporal intensity designates an intensity detected in each temporal interval d ⁇ w .
  • the temporal decomposition can be carried out by an application of a Mellin-Laplace transform to the temporal distribution I T ( ⁇ i ) , or by the application of slotted time windows (or other types of windows temporal).
  • a Mellin-Laplace transform to the temporal distribution I T ( ⁇ i )
  • slotted time windows or other types of windows temporal.
  • the time reference of the measurements is given by the measurement instants T , spaced from a few minutes to several hours.
  • Each measurement instant is broken down into temporal intensities I w , T ( ⁇ i ) for successive instants ⁇ w , ⁇ w +1 close together with a duration of a few tens of ps or hundreds of picoseconds (ps), for example 200 ps .
  • ⁇ w corresponds to a detection time interval d ⁇ w extending on either side of the detection instant ⁇ w .
  • Step 120 Explanation of the differential concentration.
  • step 110 we determine, from each temporal intensity resulting from step 110, a concentration c w , k of hemoglobin 22 k in each elementary layer l w crossed by the photons detected in the time window of rank w , extending around the detection instant ⁇ w .
  • ⁇ a,w,T ( ⁇ i ) corresponds to a variation of the absorption coefficient, at the wavelength ⁇ i , determined according to the time window of rank w , between the measurement instant T and the reference instant T ref :
  • L w is the mean free path of photons selected on ⁇ w .
  • step 120 includes a comparison, in each time window of rank w, between an intensity I w , T ( ⁇ i ) and a reference intensity I w, ref ( ⁇ i ), established, for the same window temporal, respectively from the temporal distributions I T ( ⁇ i ) and I ref ( ⁇ i ) .
  • ⁇ c w,k,T corresponds to a variation in the hemoglobin concentration, corresponding to the time window of rank w, between the measurement instant T and the reference instant T ref . Subsequently, ⁇ c w,k,T is referred to as “apparent differential concentration”.
  • each value ⁇ c w,k can be assimilated to an apparent differential concentration, the term "apparent" designating the fact that it is estimated on the basis of an assumption of homogeneity of the concentration of hemoglobin in the sample, up to depth d w .
  • each differential concentration is used, in steps 130 and 140, to segment the sample between a first layer 20 1 and a second layer 20 2 , the concentration of hemoglobin in each layer thus segmented being considered homogeneous.
  • the quantity of interest ⁇ w,k is proportional to a variation in the apparent differential concentration ⁇ c w,k of the elementary layer l w between the reference instant and the measurement instant.
  • the quantity ⁇ w,k can be considered as an apparent surface concentration. It corresponds to the apparent concentration c w,k multiplied by the mean free path of photons L w .
  • the quantity ⁇ w,k is equivalent to an apparent surface concentration, obtained as the contribution of the medium between the surface to the elementary layer of order w.
  • Step 130 comparison of the quantities of interest ⁇ w,k resulting from step 120.
  • the invention consists of comparing these quantities of interest ⁇ w,k obtained by respectively considering two elementary layers l w of different ranks.
  • the quantity ⁇ w , w ' ( ⁇ w , k ) represents a variation, as a function of w , of the quantity of interest ⁇ w , k between the elementary layer l w and the elementary layer of base l w' .
  • step 110 From the temporal intensities resulting from step 110, it is possible to calculate, for different measurement instants T, a differential quantity of interest ⁇ w , w ' ( ⁇ w , k ) for different elementary layers ⁇ w, k d' order w.
  • steps 100 to 130 are implemented at different measurement times, it is possible to obtain, for each elementary layer of rank w , a profile tracing the temporal evolution of the differential quantity of interest ⁇ w , w ' ( ⁇ w , k ).
  • the decorrelation between the superficial layer and the deep layer is easier to detect on the basis of such a profile.
  • the decorrelation between the values of ⁇ w , w ' ( ⁇ w , k ) obtained respectively between the surface layer and the deep layer can be determined visually, by a user of the device.
  • a correlation indicator is calculated, which makes it possible to quantify a correlation between two values of ⁇ w , w ' ( ⁇ w , k ) for two layers of different rank w.
  • This may be a correlation coefficient r 2 .
  • the higher the value of the correlation indicator the closer the values of ⁇ w , w ' ( ⁇ w , k ), for two layers of different rank w , are.
  • the correlation indicator between two elementary layers l w of different ranks w crosses a predetermined threshold, below which it is considered that there is a decorrelation.
  • step 120 different temporal intensities I w were extracted by applying temporal segmentation functions by applying a Mellin Laplace transform. During this step, we considered a total number W of time intervals equal to 20.
  • this is an arterial occlusion.
  • k 2
  • the quantities of interest ⁇ w , k which are proportional to a variation in the concentration of oxyhemoglobin (or deoxyhemoglobin) between the measurement instant and the reference instant, translate, during arterial clamping in this example, a decrease in the concentration of oxyhemoglobin and a slight increase in the concentration of deoxyhemoglobin.
  • the temporal profiles represented on the Figures 5B to 5E allow detection of the occurrence of an arterial occlusion from the differential quantities of interest ⁇ w,w' ( ⁇ w,k ) .
  • the detection of the occurrence of an occlusion can be carried out visually, or by calculating a correlation indicator between the values of ⁇ w, w' ( ⁇ w , k ) between elementary layers of different orders w.
  • Each differential quantity of interest is representative of a spatiotemporal variation of a concentration of oxyhemoglobin or deoxyhemoglobin.
  • the temporal variation corresponds to the term ⁇ w , k , which represents a variation of ⁇ w,k between two different times (measurement instant and reference instant).
  • the spatial variation comes from the difference between the quantities ⁇ w , k between the layer of rank w and the layer of rank w '.
  • FIG. 6A shows a correlation indicator between profiles of the figure 5D corresponding to different ranks w.
  • the x-axis and the y-axis correspond to a rank w.
  • the gray level corresponds to the correlation coefficient.
  • the Figure 6B shows a correlation indicator between profiles of the Figure 5E corresponding to different ranks w.
  • FIG. 6C is a synthesis Figures 6A and 6B : it represents the product of the correlation coefficients presented in Figure 6A and 6B .
  • Figure 6C we observe a good correlation of elementary layers 1 to 11, as well as elementary layers 13 to 20.
  • Step 140 temporal segmentation
  • Step 150 estimation of a variation in hemoglobin concentration in the deep layer 20 2 , between the measurement instant and the reference instant.
  • L 1 corresponds to the average free path in layer 20 1 : L 1 corresponds to an average of the mean free paths of the photons contributing to I 1 T and I 1 , ref . L 1 is shown on the figure 4A . Likewise, L 2 corresponds to the mean free path in layer 20 2 . L 2 corresponds to an average of the mean free paths of the photons contributing to I 2,T and I 2, ref
  • the matrix ⁇ 1 ⁇ 1 ⁇ 2 ⁇ 1 ⁇ 1 ⁇ 2 ⁇ 2 ⁇ 2 is known and that the quantities ⁇ ln I 1 , T I 1 , ref ⁇ 1 And ⁇ ln I 1 , T I 1 , ref ⁇ 2 , ⁇ ln I 1 , T I 1 , ref ⁇ 2 And ⁇ ln I 1 , T I 1 , ref ⁇ 2 result from the temporal distributions measured at the measurement instant and at the reference instant, at each wavelength, we obtain L ⁇ 2 ⁇ c 2.1 ⁇ c 2.2 , that is to say quantities L 2 ⁇ c 2.1 and L 2 ⁇ c 2.2 , proportional to the variations in concentrations ⁇ c 2.1 and ⁇ c 2.2 respectively of oxyhemoglobin and deoxyhemoglobin in the second layer 20 2 .
  • the mean free path L 2 can be estimated.
  • Steps 140 and 150 were implemented so as to estimate, at each measurement instant, quantities L 2 ⁇ c 2.1 and L 2 ⁇ c 2.2 respectively proportional to the variations in concentrations of oxyhemoglobin and deoxyhemoglobin between each measurement instant and the reference instant.
  • FIG. 7A represents estimates, over time, of concentrations of oxyhemoglobin and deoxyhemoglobin resulting respectively from an implementation of a time-resolved diffuse reflectance spectrometry method without taking into account the surface layer (curves a and b respectively ) and an implementation of a time-unresolved diffuse reflectance spectrometry method, according to the prior art (curves c and d).
  • Figure 7A is representative of an arterial occlusion.
  • FIG. 7B represents variations in concentrations of oxyhemoglobin (curve a) and deoxyhemoglobin (curve b) illustrated in the Figure 7A , corrected according to the implementation of the invention as well as temporal smoothing of the concentrations estimated at different measurement times.
  • the ordinate axis corresponds to the variations in concentrations of oxyhemoglobin and deoxyhemoglobin, in layer 20 2 , multiplied by L 2 : this is L 2 ⁇ c 2.1 and L 2 ⁇ c2.2 .
  • Licox registered trademark
  • a Licox probe known to those skilled in the art, makes it possible to measure a partial pressure of oxygen in the tissues.
  • FIG. 8A represents an estimate of the variation in concentration of oxyhemoglobin (curve a) and deoxyhemoglobin (curve b), each variation being multiplied by L 2 , resulting from the implementation of steps 100 to 150, during an arterial occlusion.
  • curve c A curve resulting from the Licox probe (curve c) is also shown.
  • FIG. 8B represents an estimate of the variation in concentration of oxyhemoglobin (curve a) and deoxyhemoglobin (curve b), each variation being multiplied by L 2 , resulting from the implementation of steps 100 to 150, during venous occlusion.
  • a curve resulting from the Licox probe (curve c) is also shown.
  • a Licox probe does not allow us to estimate a concentration variation. Additionally, it is an invasive measure.
  • the Licox probe makes it possible to detect the occurrence of an occlusion, whether it is an arterial or venous occlusion, without being able to discriminate the type of occlusion. It is observed that the measurements according to the invention, non-invasive, are consistent with the Licox measurements to detect the occurrence of an occlusion. They allow an estimation of a variation in the concentration of oxyhemoglin and deoxyhemoglobin compared to a reference moment. We can thus identify the type of occlusion: arterial or venous.

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Claims (7)

  1. Verfahren zur Überwachung der Vaskularisierung eines biologischen Gewebes zwischen mindestens einem Messzeitpunkt (T) und einem Bezugszeitpunkt (Tref), wobei das biologische Gewebe von einer Oberfläche (21) begrenzt wird, wobei das biologische Gewebe eine Oberflächenschicht (201) und eine tiefe Schicht (202) enthält, wobei die Oberflächenschicht sich zwischen der Oberfläche des Gewebes und der tiefen Schicht erstreckt, wobei das Verfahren aufweist:
    - a) Beleuchtung des biologischen Gewebes durch eine Impulslichtquelle (10), wobei die Lichtquelle gegenüber der Oberfläche des biologischen Gewebes angeordnet ist, wobei die Lichtquelle einen Beleuchtungsstrahl (11) emittiert, der eine Beleuchtungszone (12) an der Oberfläche des biologischen Gewebes bildet, wobei der Beleuchtungsstrahl gleichzeitig oder nacheinander auf zwei voneinander unterschiedlichen Beleuchtungswellenlängen emittiert wird, wobei jede Wellenlänge sich in einem Absorptionsspektralband von Oxyhämoglobin und/oder von Desoxyhämoglobin erstreckt;
    - b) bei jeder Wellenlänge, Erkennung von vom biologischen Gewebe rückgestreuten Photonen, nachdem sie sich im biologischen Gewebe ausgebreitet haben, durch einen Photodetektor (16), wobei die erkannten rückgestreuten Photonen von einer Erkennungszone (14) an der Oberfläche des biologischen Gewebes kommen ;
    - c) bei jeder Wellenlänge, Erhalt einer zeitlichen Verteilung (IT(λi), IRef(λi)), die eine Anzahl von vom Photodetektor abhängig von der Zeit erkannten Photonen darstellt, wobei die zeitliche Verteilung sich gemäß einer Dauer ausgehend von einem Ursprungszeitpunkt erstreckt;
    wobei die Schritte a) bis c) zum Bezugszeitpunkt und zum Messzeitpunkt oder zu jedem Messzeitpunkt ausgeführt werden ;
    wobei das Verfahren dadurch gekennzeichnet ist, dass es zum Messzeitpunkt oder zu jedem Messzeitpunkt und zum Bezugszeitpunkt aufweist:
    - d) Segmentierung der Dauer jeder zeitlichen Verteilung in Erkennungsintervalle (dτ w ), wobei jedem Erkennungsintervall ein Rang (w) zugeordnet ist, wobei der Rang um so höher ist, je weiter das Erkennungsintervall vom Ursprungszeitpunkt der zeitlichen Verteilung entfernt ist, wobei jedes Erkennungsintervall einer Elementarschicht (lw ) zugeordnet ist, die sich in einer Tiefe (dw) im biologischen Gewebe erstreckt;
    - e) für jede Elementarschicht (lw ), ausgehend von jeder aus c) resultierenden zeitlichen Verteilung, die zum Messzeitpunkt und zum Bezugszeitpunkt erstellt werden, Bestimmung von zeitlichen Intensitäten (Iw,T, Iw,ref), entsprechend einer Anzahl von während jedes Erkennungsintervalls (dτw) erkannten Photonen ;
    und dass es zum Messzeitpunkt oder zu jedem Messzeitpunkt aufweist
    - f) für jedes Erkennungsintervall (dτw), Berechnung eines Verhältnisses zwischen der zeitlichen Intensität zum Messzeitpunkt und der zeitlichen Intensität zum Bezugszeitpunkt ;
    - g) ausgehend von den aus f) resultierenden Verhältnissen, die für jede Wellenlänge erstellt werden, Berechnung einer interessierenden Größe (Δξw,k) für jede jedem Erkennungsintervall zugeordnete Elementarschicht, wobei die interessierende Größe für eine Änderung der Konzentration von Hämoglobin in der Elementarschicht zwischen dem Messzeitpunkt und dem Bezugszeitpunkt repräsentativ ist ;
    - h) für jede Elementarschicht (lw ), Vergleich der in g) berechneten interessierenden Größe mit einer interessierenden Basisgröße, berechnet für eine Basiselementarschicht, wobei die Basiselementarschicht eine der Elementarschichten des biologischen Gewebes ist, um für jede Elementarschicht eine differenzielle interessierende Größe (δw,w'(Δξw,k) zu erhalten;
    - i) Bestimmung einer Entwicklung, gemäß der Tiefe des biologischen Gewebes, der differenziellen interessierenden Größen (δw,w'(Δξw,k).
  2. Verfahren nach einem der vorhergehenden Ansprüche, wobei:
    - die Schritte a) bis h) zu verschiedenen Messzeitpunkten durchgeführt werden ;
    - der Schritt i) eine Bildung eines Profils für jede Elementarschicht (l w) aufweist, wobei jedes Profil eine Änderung der interessierenden differenziellen Größe (δw,w'(Δξw,k)) in der Elementarschicht abhängig vom Messzeitpunkt (T) darstellt;
    - der Schritt i) eine Berechnung eines Korrelationskriteriums zwischen verschiedenen Profilen aufweist, die verschiedenen Elementarschichten entsprechen, wobei das Korrelationskriterium eine Korrelation zwischen den verschiedenen Profilen ausdrückt.
  3. Verfahren nach Anspruch 2, das nach i) aufweist:
    - j) Bestimmung einer Schnittstellen-Elementarschicht (l w1/2), ausgewählt unter den verschiedenen Elementarschichten, wobei die Schnittstellen-Elementarschicht eine Schicht ist, auf deren beiden Seiten das Korrelationskriterium den Schwellwert überschreitet, wobei die Schnittstellen-Elementarschicht als eine Schnittstelle zwischen der Oberflächenschicht (201) und der tiefen Schicht (202) bildend angesehen wird, wobei die Schnittstellen-Elementarschicht einem zeitlichen Schnittstellenintervall (dτ1/2) zugeordnet ist ;
    - k) zum Bezugszeitpunkt und zu einem Messzeitpunkt, ausgehend von jeder aus c) resultierenden zeitlichen Verteilung c), die zum Messzeitpunkt erstellt wird, Berechnung :
    • einer ersten zeitlichen Intensität (I1,T(λi)), die einen Beitrag zur zeitlichen Verteilung von vor dem zeitlichen Schnittstellenintervall erkannten Photonen aufweist, wobei von den Photonen angenommen wird, dass sie sich nur in der Oberflächenschicht ausgebreitet haben ;
    • einer zweiten zeitlichen Intensität (I2,T(λi)), die einen Beitrag zur Verteilung von nach dem zeitlichen Schnittstellenintervall erkannten Photonen aufweist, wobei von den Photonen angenommen wird, dass sie sich in der Oberflächenschicht und in der tiefen Schicht ausgebreitet haben ;
    - I) Berechnung eines ersten Verhältnisses I 1 , T I 1 , ref λ i
    Figure imgb0025
     ausgehend von den ersten im Bezugszeitpunkt bzw. Messzeitpunkt bestimmten zeitlichen Intensitäten und Berechnung eines zweiten Verhältnisses I 2 , T I 2 , ref λ i
    Figure imgb0026
     ausgehend von den zweiten im Bezugszeitpunkt bzw. Messzeitpunkt bestimmten zeitlichen Intensitäten ;
    - m) Schätzung der Änderungen der Konzentrationen von Oxyhämoglobin und von Desoxyhämoglobin (Δc2,1, Δc2,2) oder von Größen proportional zu den Änderungen ( L 2Δc 2,1, L 2Δc 2,2) in der tiefen Schicht (202) zwischen dem Messzeitpunkt und dem Bezugszeitpunkt ausgehend von den aus I) resultierenden Verhältnissen.
  4. Verfahren nach Anspruch 3, das aufweist:
    - o) Schätzung der Änderungen der Konzentrationen von Oxyhämoglobin und von Desoxyhämoglobin (Δc1,1, Δc1,1) oder von Größen proportional zu den Änderungen ( L 1Δc 1,1, L 1Δc 1,2) in der Oberflächenschicht (201) zwischen dem Messzeitpunkt und dem Bezugszeitpunkt ausgehend von den aus m) resultierenden Verhältnissen.
  5. Verfahren nach einem der vorhergehenden Ansprüche, wobei im Schritt h) die Basisschicht ist :
    - eine vorbestimmte Elementarschicht ;
    - oder eine Elementarschicht eines anderen Rangs als die betrachtete Elementarschicht, wobei die Abweichung zwischen dem Rang der Basiselementarschicht und der betrachteten Elementarschicht konstant ist.
  6. Verfahren nach einem der vorhergehenden Ansprüche, wobei die Lichtquelle eine Laserquelle ist.
  7. Vorrichtung, dazu bestimmt, ein Auftreten eines Venen- oder Arterienverschlusses in einem biologischen Gewebe (20) zwischen mindestens einem Messzeitpunkt (T) und einem Bezugszeitpunkt (Tref) zu erkennen, wobei das biologische Gewebe von einer Oberfläche (21) begrenzt wird, wobei die Vorrichtung aufweist:
    - eine Impulslichtquelle (10), wobei die Lichtquelle gegenüber der Oberfläche des biologischen Gewebes angeordnet ist, wobei die Lichtquelle konfiguriert ist, einen Beleuchtungsstrahl (11) zu emittieren, der eine Beleuchtungszone (12) an der Oberfläche des biologischen Gewebes formt, wobei die Lichtquelle konfiguriert ist, gleichzeitig oder nacheinander den Beleuchtungsstrahl auf zwei voneinander unterschiedlichen Beleuchtungswellenlängen zu emittieren, wobei jede Wellenlänge sich in einem Absorptionsspektralband des Oxyhämoglobins und/oder des Desoxyhämoglobins erstreckt;
    - einen Photodetektor (16), der konfiguriert ist, vom biologischen Gewebe rückgestreute Photonen zu erkennen, nachdem sie sich im biologischen Gewebe ausgebreitet haben, wobei die rückgestreuten Photonen von einer Erkennungszone (14) an der Oberfläche des biologischen Gewebes kommen ;
    - eine Zählkarte (17), dazu bestimmt, eine zeitliche Verteilung (IT(λi), IRef(λi)) zu erstellen, die eine Anzahl von vom Photodetektor auf jeder Wellenlänge abhängig von der Zeit erkannten Photonen darstellt;
    - eine Verarbeitungseinheit (18), die programmiert ist, die Schritte d) bis i) eines Verfahrens nach einem der vorhergehenden Ansprüche ausgehend von den von der Zählkarte auf jeder Wellenlänge erstellten zeitlichen Verteilungen zum Messzeitpunkt oder zu jedem Messzeitpunkt durchzuführen.
EP21217909.7A 2020-12-29 2021-12-28 Verfahren zur analyse einer probe durch zeitlich aufgelöste messung der intensität von rückgestreuten photonen Active EP4023147B1 (de)

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